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Activation of caspase-8 contributes to 3,3 '-diindolylmethane-induced apoptosis in colon cancer cells

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Authors
Kim, Eun Ji; Park, So Young; Shin, Hyun-Kyung; Kwon, Dac Young; Surh, Young-Joon; Park, Jung Han Yoon
Issue Date
2007-01
Citation
Journal of Nutrition, Vol.137 No.1, pp.31-36
Abstract
3,3'-Diindolylmethane (DIM) is the major in vivo product of acid-catalyzed oligomerization of indole-3-carbinol, which is a promising anticancer agent present in cruciferous vegetables and has itself been reported to have anticarcinogenic properties. This study examined DIM-mediated regulation of apoptosis in the HCT116 (wild-type p53) and HT-29 (mutant p53) human colon cancer cell lines. DIM (0-30 mu mol/L) substantially decreased the number of viable cells and induced apoptosis of HCT116 and HT-29 cells in a concentration-dependent manner, Western-blot analyses of total cell lysates revealed that DIM increased the activation of caspase-3, -7, -8, and -9 and enhanced poly(ADP-ribose) polymerase cleavage in both HCT116 and HT-29 cells. In addition, DIM increased the translocation of cytochrome c and Smac/Diablo from the mitochondria to the cytoplasm. In concert with the caspase-8 activation by DIM, increased levels of Fas and truncated Bid were observed. DIM did not affect the protein levels of p53, BcI-2, Bax, or Fas ligand (FasL) in HCTl 16 cells. In HT-29 cells, however, DIM decreased BcI-2 levels, although the protein levels of Bax or FasL were not affected. The caspase-8 inhibitor Z-IETD-FMK attenuated the DIM-induced apoptosis, indicating that increased activation of this enzyme contributed to the increase in p53-independent apoptosis that was observed in colon cancer cells. We have demonstrated that DIM induces apoptosis in colon cancer cells, providing insights into the mechanisms underlying its antitumorigenic activities. J. Nutr. 137: 31-36, 2007.
ISSN
0022-3166
URI
https://hdl.handle.net/10371/172799
DOI
https://doi.org/10.1093/jn/137.1.31
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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